LUNG cancer in never smokers is emerging as a major global health concern, with patterns that differ strikingly from smoking-related disease. This group often falls outside traditional high-risk criteria, meaning symptoms may be overlooked and many patients are diagnosed only once cancer has spread, when treatment is mainly palliative. In a recent opinion article, experts argue that lung cancer in never smokers requires a different approach to detection and prevention.
Lung cancer in never smokers tends to affect women and Asian populations more frequently and is usually an adenocarcinoma with so‑called “oncogene-addicted” tumours driven by mutations or fusions in genes such as EGFR and ALK. These cancers often carry multiple actionable driver mutations but a lower overall mutational burden, which helps explain why they respond well to tyrosine kinase inhibitors yet much less to standard immune checkpoint inhibitors.
Complex Mix of Genetic and Environmental Risks
The opinion article highlights a web of inherited and acquired risk factors rather than a single cause. Germline variants in oncogenes and DNA repair genes, APOBEC3A/B deletions, and clonal haematopoiesis can all increase susceptibility, sometimes at a young age and with multifocal lung lesions. Environmental exposures (radon, diagnostic and environmental radiation, second‑hand smoke, air pollution, and some inflammatory conditions) add further risk, often with only modest individual effect sizes but substantial combined population impact.
This complexity makes it difficult to build robust risk algorithms or justify broad, expensive screening programmes in never smokers. Current data discussed in the article suggest that carefully selected high‑risk groups, such as Asian women with a family history of lung cancer, may benefit from low‑dose CT screening, but survival and cost‑effectiveness evidence remains limited.
Early Detection and Prevention of Lung Cancer in Never Smokers
Because lung cancer in never smokers has a high rate of targetable mutations and distinct immune features, the authors argue it needs tailored research and clinical pathways. Trials are exploring earlier use of EGFR‑ and ALK‑targeted therapies, preventive or perioperative cancer vaccines aimed at neoantigens, and immunotherapy in high‑risk pre‑cancer settings.
These strategies, presented in the opinion article, must balance potential gains in mortality reduction against toxicity, immune‑related adverse events and health‑system cost. For now, clinicians are encouraged to maintain a high index of suspicion for lung cancer in never smokers with persistent symptoms, while research moves towards more precise risk stratification, screening, and prevention for this under‑recognised patient group.
Reference
Caswell DR et al. Lung cancer in never smokers: from early detection to prevention. Trends Cancer. 2026; DOI:10.1016/j.trecan.2025.12.009.
